Beta‐cryptoxanthin supplementation inhibits NNK‐induced lung tumor multiplicity via inhibition of α7 nicotinic receptor expression and AKT activation in A/J mice

The efficacy of beta‐cryptoxanthin (BC) for lung carcinogenesis has not been studied despite its association with a reduced risk of lung cancer in epidemiological studies. The activation of nicotinic acetylcholine receptor α7 subunit (α7‐nAChR) and its downstream pathway can promote lung tumor growth. We hypothesize that BC prevents the tobacco carcinogen‐induced lung tumorigenesis by targeting α7‐nAChR signaling. Male A/J mice were randomly assigned to six groups (n=16): the experimental arm received the NNK injection with or without supplementation with BC at two doses (0.2 and 2 mg/kg/d); and the control arm without NNK injection received the same BC treatments. The incidence and multiplicity of lung tumor and α7‐nAChR expression and AKT activation were examined after 16 wk post the carcinogen injection. There were 52% and 63% reductions of lung tumor multiplicity in mice supplemented with BC at two doses, respectively (P <0.001), as compared to the NNK alone group. The reduced‐tumor multiplicity by BC was associated with the suppressions of the NNK‐induced α7‐nAChR expression, AKT activation, and cyclin D1 protein, measured by real‐time PCR and immunoblotting. By HPLC analysis, a significant amount of BC was detected in the livers of the mice with BC treatment. These results suggest that BC is an effective chemopreventive agent for prevention of lung carcinogenesis. (Supported by NIH grant R01CA104932) Grant Funding Source: R01CA104932